ABSTRACT: Transgenic and ES Cell Core The Transgenic and ES Cell Core of the Washington University Diabetes Research Center (DRC) provides services for efficient and cost-effective development of genetically altered mouse models to elucidate the pathogenesis of diabetes and related metabolic disorders. Importantly, in vivo models allow analysis of gene function in the context of complex intercellular and integrative systemic responses needed for the study of diabetes, a polygenic disorder involving multiple tissue types and environmental influences. Current molecular genetic techniques allow spatially and temporally restricted analysis of gene effects (both inactivation and over- expression) in mice, leading to previously unprecedented creativity and analytical resolution. The concepts involved in generating transgenic (Tg) or knockout/knockin (KO/KI) animals are straightforward. However, it is impractical and too expensive for most labs to maintain the requisite equipment, facilities, and highly skilled personnel for making genetically altered mice. Given the substantial demand by the Washington University community for assistance in the generation of these mouse models, the DRC Transgenic and ES Cell Core will continue to provide the necessary advice, expertise, facilities, equipment, and personnel to efficiently generate Tg and KO/KI mice for DRC members using state-of-the-art techniques, such as CRISPR/Cas9 nuclease- mediated genome editing in ES cells and in mouse zygotes. The Core will also assist in propagating poorly breeding animals, and in achieving transient Cre or FLP recombinase expression in zygotes by microinjection of expression plasmids. By making specialized, state-of-the-art services accessible to DRC investigators, the Core facilitates translation of basic research advances toward improvements in the diagnosis, treatment and cure of diabetes.